Characterization of the phagosome during Mycobacterium tuberculosis infection

结核分枝杆菌感染过程中吞噬体的表征

• 批准号: 7776899
• 负责人: DAWN L NOLT
• 金额: $ 13.03万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-03-01 至 2013-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7776899
• 关键词: Abbreviations; Advisory Committees; Antigen Presentation Pathway; Antigen-Presenting Cells; Antigens; Area; Bacteria; Biotinylation; Brefeldin A; CD8B1 gene; Cells; Cellular biology; Characteristics; Communicable Diseases; Complex; Cross Presentation; Cytosol; Data; Dendritic Cells; Derivation procedure; Destinations; Development; Electron Microscopy; Endoglycosidases; Endoplasmic Reticulum; Environment; Future; Goals; Green Fluorescent Proteins; HLA Antigens; Health Sciences; Human; Immune response; Immunity; Immunology; Infection; Interferon Type II; Knowledge; MHC antigen; Major Histocompatibility Complex; Mediating; Medical; Mentors; Methods; Microscopy; Mission; Morbidity - disease rate; Mycobacterium tuberculosis; National Institute of Allergy and Infectious Disease; Oregon; Organelles; Pathway interactions; Pediatrics; Peripheral Blood Mononuclear Cell; Phagocytosis; Phagosomes; Phenotype; Physicians; Phytohemagglutinins; Population; Postdoctoral Fellow; Production; Program Development; Protein Disulfide Isomerase; Public Health; Quality Control; RNA; Recycling; Research; Research Personnel; Resources; Role; Scientist; Small Interfering RNA; Spottings; Structure; Surface; T cell response; T-Lymphocyte; Techniques; Time; Training; Training Programs; Tuberculosis; Universities; Vaccines; Western Blotting; antigenic peptide transporter; base; beta-2 Microglobulin; career; design; glycosylation; graduate student; immune function; immunogenic; interest; knowledge base; macrophage; mortality; pathogen; pediatric department; receptor; skills; tapasin; therapeutic vaccine; trafficking; trans-Golgi Network; vaccine candidate

This proposal describes a 5-year training program for the development of an academic career in infectious diseases (ID). The applicant has completed training in both pediatrics and ID. Her goal during the next 5 years is to develop the skills necessary to succeed as an independent scientific investigator in the fields of human immunology and cellular biology. The applicant's interest in ID prompted her research towards Mycobacterium tuberculosis (Mtb). This pathogen infects 1/3 of the world's population and is an enormous global burden. The CD8+ T cell response is increasingly recognized as important in the immune response against Mtb. Once internalized by cells, Mtb resides within a structure called the phagosome. Our preliminary data suggests that the phagosome may participate in MHC l-mediated "cross-presentation" of Mtb-specific antigens to CD8+ T cells. The long-term goal is to investigate the role of the phagosome in Mtb infection. The specific aims are: (1) Is the phagosome a MHC-I presenting organelle for Mtb? (2) Is the MHC-I molecule within the phagosome derived from the endoplasmic reticulum or recycled from the surface? Dr. David Lewinsohn will mentor the applicant's scientific development. Dr. Lewinsohn is a recognized leader in the field of human immunology against Mtb and has trained numerous postdoctoral fellows and graduate students. In addition, an advisory committee of highly-regarded medical scientists will provide scientific and career advice. The Pediatrics department at Oregon Health & Science University is a very collaborative environment and provides an ideal setting for training physician-scientists. The incorporation of expertise from diverse resources maximizes the potential for the applicant to establish a scientific basis from which an academic career can be founded. Relevance to public health: Mtb remains a significant contributor to morbidity and mortality worldwide. Our studies will advance knowledge in key areas of Mtb immunology, particularly regarding CD8+ T cells. Since a future vaccine against Mtb will likely need to include CD8+ T cell responses, our findings will guide the design and development of vaccine candidates. This proposal furthers the mission of the NIAID in determining better means of controlling Mtb, a pathogen with immense global impact.

该提案描述了一个为期5年的培训计划，以发展传染病的学术职业 疾病（ID）。申请人已经完成了儿科和ID的培训。她在接下来的5个目标中的目标 多年是发展成为成功成为独立科学研究者所必需的技能 人类免疫学和细胞生物学。申请人对ID的兴趣促使她研究 结核分枝杆菌（MTB）。这种病原体感染了世界人口的1/3，是一个巨大的 全球负担。 CD8+ T细胞反应越来越被认为在免疫反应中很重要 反对MTB。一旦被细胞内化，MTB就位于称为吞噬体的结构内。我们的初步 数据表明，吞噬体可能参与MTB特异性的MHC L介导的“交叉表现” CD8+ T细胞的抗原。长期目标是研究吞噬体在MTB感染中的作用。 具体目的是：（1）吞噬体是MTB的MHC-I呈现细胞器吗？ （2）是MHC-I 源自内质网的吞噬体中的分子或从表面回收的分子？ David Lewinsohn博士将指导申请人的科学发展。 Lewinsohn博士是公认的 针对MTB的人类免疫学领域的领导者，并培训了许多博士后研究员和 研究生。此外，由备受瞩目的医学科学家的咨询委员会将提供 科学和职业建议。 俄勒冈州健康与科学大学的儿科系是一个非常协作的环境， 为培训医师科学家提供了理想的设置。从多元化的专业知识合并 资源最大化申请人建​​立科学基础的潜力 职业可以建立。 与公共卫生有关：MTB仍然是全球发病率和死亡率的重要贡献。我们的 研究将促进MTB免疫学关键领域的知识，特别是关于CD8+ T细胞的知识。自从 对MTB的未来疫苗可能需要包括CD8+ T细胞反应，我们的发现将指导 候选疫苗的设计和开发。该提议进一步推进了Niaid的使命 确定控制MTB的更好手段，MTB是具有巨大全球影响的病原体。